Diagnostic Imaging Pathways - Iodinated Intravascular Contrast Media

In Australia, intravascular contrast media for radiographic procedures are almost exclusively non-ionic (as opposed to ionic) contrast agents. Non-ionic agents are thought to be up to 10 times safer than ionic contrast media. Uses of contrast include intravenous urography, contrast-enhanced CT scans, venography and angiography.

Allergic-Like Reactions

The vast majority of patients tolerate intravascular non-ionic contrast injection well. Severe reactions including shock from anaphylactoid reactions do occur very rarely in about 1 in every 25,000 injections. The risk of a fatal reaction is estimated at 1 in 170,000. These reactions are not dose-dependent and do not involve antibody formation to contrast media. The clinical features of anaphylactoid reactions usually manifest within 60 minutes, with the majority developing in the first 5 minutes. Delayed reactions occur up to one week post-injection and generally involve skin rashes without bronchospasm or laryngeal oedema. Symptoms vary between patients and can be classified into system-based categories:

• Cutaneous
  • Generalised pruritus, flushing
  • Urticaria (hives) or angioedema
• Respiratory
  • Laryngeal oedema (hoarseness, stridor)
  • Bronchospasm (shortness of breath, wheezing)
  • Respiratory failure
• Cardiovascular
  • Arrhythmias
  • Conduction disturbances
  • Vasodilatation, increased vascular permeability
  • Hypotension, anaphylactic shock
• Neurological
  • Syncope, dizziness
  • Seizures
• Gastrointestinal
  • Nausea, vomiting, diarrhoea
  • Abdominal cramps

While the risk of severe reaction is largely unpredictable, factors that predispose to a reaction include: a history of a previous generalized contrast reaction, an atopic history and a history of asthma. B-blockers have also been shown to increase the risk of anaphylactoid reactions and bronchospasm (This population may be resistant to adrenaline used in resuscitation and IM glucagon should be used if adrenaline is ineffective). Patients at risk should receive non-ionic contrast agents if iodinated contrast material is needed. Use of pre-medication is variable and opinion is divided. Corticosteroids +/- antihistamines (eg prednisolone 50mg orally taken 13 and 1 hour(s) before contrast administration +/- diphenhydramine 50mg 1 hour before contrast) have been the most widely recommended agents but are not effective if commenced less than 6 hours before the procedure. 1, 11 There is also insufficient evidence to show that pre-medication decreases the incidence of life-threatening reactions. 2
The feeling of warmth and a metallic taste is relatively common with administration of intravenous contrast and does not indicate that an allergic reaction has occurred. Patients should be made aware of the potential risks of contrast media prior to the procedure. 3

Contrast Induced Nephropathy

The use of intravenous contrast medium in radiological examinations carries an overall risk of contrast-induced nephropathy of approximately 1.2-2.7%. Contrast-induced nephropathy is defined as impairment of renal function indicated by a rise in serum creatinine by more than 25% occuring within 3 days of IV contrast administration in the absence of another aetiology. Most cases recover spontaneously within 14 days although a minority can progress to chronic renal failure and dialysis. The factors that increase the risk of intravascular contrast media-induced nephropathy with a marked decline in renal function include:

• Underlying renal impairment (plasma creatinine >132 mmol/L) or renal disease
• Diabetes Mellitus
• Age > 70 years
• Use of nephrotoxic medications (eg NSAIDS, diuretics, ACE inhibitors, aminoglycosides, amphotericin, antineoplastics, cyclosporin, lithium, methotrexate, vancomycin)
• Cardiac failure
• Hypertension
• Gout
• Dehydration
• Previous renal surgery
• Cirrhosis of the liver
• Intra-arterial contrast administration, large doses of contrast and repeated doses of contrast

Renal function can be assessed by using the plasma/serum creatinine and estimating creatine clearance using the Cockcroft-Gault equation (shown below). The Modified Diet in Renal Disease (MDRD)-derived eGFR commonly reported in association with serum creatinine in laboratory reports does not take into account patient weight and is unreliable for those who are extremely overweight or underweight. 10

The Cockcroft-Gault formula is: 4
Creatinine Clearance = {(140 - age) x weight / serum creatinine x 814}
* multiply by 0.85 for women
* Weight is measured in kg, [serum creatinine] in mmol/L, creatinine clearance in mL/min.
* Normal creatinine clearance is 95 ± 20 mL/min in women and 120 ± 25 mL/min in men.

The probability of developing contrast induced nephropathy requiring dialysis varies according to the pre-existing renal impairment. 5

Evidence suggests that a small, transient rise in plasma creatinine is relatively common following administration of intravenous contrast media. Patients with normal or borderline-normal renal function generally do not require precautionary measures. In patients with a plasma/serum creatinine of >250-300mmol/L, iodinated contrast is contraindicated and should be avoided. For patients with a plasma/serum creatinine >150mmol/L, strategies to reduce the risk of contrast nephropathy include: 3,6

• Considering alternatives to the use of IV iodinated contrast, such as non-contrast CT, ultrasound, or MRI.
• Use of low osmolality or iso-osmolar contrast media
• Hydration: intravenous hydration with normal saline is preferable to oral hydration at a rate of at least 1-2 mL/hr/per kg body weight and should be commenced at least 4 hours prior to the procedure and continued for 4-24 hours post procedure. This may not be appropriate in certain clinical situations (eg. congestive heart failure) and caution must be applied.
• Nephrotoxic medications should be ceased for at least 24 hours before and after where possible
• N-Acetyl Cysteine: its use is controversial and there is variable evidence regarding its reno-protective effect. A renal physician should be consulted regarding its use.
  

Patients on metformin for diabetes are at risk of metabolic lactic acidosis with intravascular contrast. This is very rare, but the risk is increased when there is co-existent renal impairment. When contrast medium administration is necessary, the metformin ideally should be ceased prior to the procedure (48 hours before when there is renal impairment), the patient kept well hydrated and the metformin restarted 48 hours following the procedure only if renal function and serum creatinine are unchanged. Patients with known renal impairment will need monitoring of renal function prior to and after the procedure. In certain severe cases, it may preclude them from receiving intravenous contrast. 7

Contrast Induced Thyrotoxicosis

Thyrotoxicosis secondary to iodinated contrast material is rare but may occur in patients with abnormal thyroid function. Patients whom manifest hyperthyroidism should not be given iodinated contrast material. Patients with Graves’ disease, multinodular goiter or other forms of thyroid autonomy, especially if they are elderly and/or live in areas of dietary iodine deficiency are at risk of iodinated contrast induced thyrotoxicosis. 8 These patients should be monitored by an endocrinologist after administration of iodinated contrast medium and in selected high-risk patients, prophylaxis prescribed by an endocrinologist may be warranted. Intravenous cholangiographic contrast media should not be given to patients at risk. 8

Iodinated Contrast Use in Pregnancy and Lactation

In exceptional circumstances, when contrast use is deemed necessary, iodinated contrast media may be given to the pregnant mother. The theoretical risk of contrast induced hypothyroidism within the foetus has not been validated and foetal exposure to iodinated contrast media and any associated free iodide is likely to be small and relatively short-lived. Although no adverse foetal effects due to contrast administration during pregnancy have been proven, current guidelines recommend that all neonates should receive thyroid function testing in the first week of life where the mother has received iodinated contrast material in accordance with current standard paediatric care. 9

European guidelines have stated that cessation of breast feeding following iodinated contrast material is not required. 9 The amount of contrast media excreted in breast milk is very small and the absorbed dose to the foetus even smaller. The likelihood of either direct toxicity or allergic reaction is therefore extremely low. However, as with other drugs and foodstuffs, the taste of milk may be altered.

References

1. European Society of Urogential Radiology. ESUR Guidelines on Contrast Media Version 5.0. 2005 [cited 2006 November 13]. (Guidelines) Click here to view reference

2. Bettman MA. Frequently asked questions: iodinated contrast agents. Radiographics 2004; 24:S3-S10. (Review Article)

3. Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology. In which patients should serum creatinine be measured before iodinated contrast medium administration? Eur Radiol 2005; 15:749-754. (Review Article)

4. Doolan, PD, Alpen, EL, Theil, GB. A clinical appraisal of the plasma concentration and endogenous clearance of creatinine. Am J Med 1962; 32:65.

5. McCullough PA, Wolyn R, Rocher LL, et al. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997;103:368-75. (Level II study)

6. Barrett BJ, Parfrey PS. Preventing nephropathy induced by contrast medium. NEJM 2006; 354:379-385. (Review Article)

7. Thomsen HS. Guidelines for contrast media from the European Society of Urogenital Radiology. AJR 2003; 181:1463-1471. (Guidelines)

8. van der Molen AJ, Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology. Effect of iodinated contrast media on thyroid function in adults. Eur Radiol 2004; 14:902-907. (Review Article)

9. Webb JAW, Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol 2005; 15:1234-1240. (Review Article)

10. Roberts, GW. Dosing of key renally cleared drugs in the elderly - Time to be wary of the eGFR. J Pharm Prac Res 2006; 36:204-209. (Review Article)

11. The Royal Australian and New Zealand College of Radiologists. RANZCR Guidelines for iodinated contrast administration. March 2009 [cited 2009 March 24]. (Guidelines) Click here to view reference

Last reviewed March 2009.

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